Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid

The introduction of type b Haemophilus influenzae conjugate vaccines into routine vaccination schedules has significantly reduced the burden of this disease; however, widespread use in developing countries is constrained by vaccine costs, and there is a need for a simple and high-yielding manufactur...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Glycoconjugate journal 2011-10, Vol.28 (7), p.463-472
Hauptverfasser: Laferriere, Craig, Ravenscroft, Neil, Wilson, Seanette, Combrink, Jill, Gordon, Lizelle, Petre, Jean
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 472
container_issue 7
container_start_page 463
container_title Glycoconjugate journal
container_volume 28
creator Laferriere, Craig
Ravenscroft, Neil
Wilson, Seanette
Combrink, Jill
Gordon, Lizelle
Petre, Jean
description The introduction of type b Haemophilus influenzae conjugate vaccines into routine vaccination schedules has significantly reduced the burden of this disease; however, widespread use in developing countries is constrained by vaccine costs, and there is a need for a simple and high-yielding manufacturing process. The vaccine is composed of purified capsular polysaccharide conjugated to an immunogenic carrier protein. To improve the yield and rate of the reductive amination conjugation reaction used to make this vaccine, some of the carboxyl groups of the carrier protein, tetanus toxoid, were modified to hydrazides, which are more reactive than the ε -amine of lysine. Other reaction parameters, including the ratio of the reactants, the size of the polysaccharide, the temperature and the salt concentration, were also investigated. Experimental design was used to minimize the number of experiments required to optimize all these parameters to obtain conjugate in high yield with target characteristics. It was found that increasing the reactant ratio and decreasing the size of the polysaccharide increased the polysaccharide:protein mass ratio in the product. Temperature and salt concentration did not improve this ratio. These results are consistent with a diffusion controlled rate limiting step in the conjugation reaction. Excessive modification of tetanus toxoid with hydrazide was correlated with reduced yield and lower free polysaccharide. This was attributed to a greater tendency for precipitation, possibly due to changes in the isoelectric point. Experimental design and multiple regression helped identify key parameters to control and thereby optimize this conjugation reaction.
doi_str_mv 10.1007/s10719-011-9344-3
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_907171885</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2469097911</sourcerecordid><originalsourceid>FETCH-LOGICAL-c402t-e9a439006f95f216d64d14cc7528e203e1d88b02e8ed2ae2d9eb51ce93c3d5903</originalsourceid><addsrcrecordid>eNp1kT1vFDEQhi0EIkfCD6BBFg2VYez9sksUJQQpUpqktnz27J1Pu_ay9obcdfxzfLoAEhKVi3ned6x5CHnH4RMH6D4nDh1XDDhnqqprVr0gK950FauVbF-SFQgpGICEM_ImpR2UTC3ka3ImuGyg6boV-Xn1NOHsRwzZDNRh8ptAc6Rxyn70B6Qm0BuDY5y2flgS9aEfFgwHgzTvJ6RramPYLRuTkT4aa31AOhqH9IfPW7rdu9kcvEPmypJHk0ujoxmzCaUrx6fo3QV51Zsh4dvn95w8XF_dX96w27uv3y6_3DJbg8gMlakrBdD2qukFb11bO15b2zVCooAKuZNyDQIlOmFQOIXrhltUla1co6A6Jx9PvdMcvy-Ysh59sjgMJmBcklbllh2Xsinkh3_IXVzmUD6npap5qzo4QvwE2TmmNGOvp3JGM-81B320o092dLGjj3Z0VTLvn4uX9YjuT-K3jgKIE5DKKGxw_rv5_62_AJFEnMQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>894169705</pqid></control><display><type>article</type><title>Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Laferriere, Craig ; Ravenscroft, Neil ; Wilson, Seanette ; Combrink, Jill ; Gordon, Lizelle ; Petre, Jean</creator><creatorcontrib>Laferriere, Craig ; Ravenscroft, Neil ; Wilson, Seanette ; Combrink, Jill ; Gordon, Lizelle ; Petre, Jean</creatorcontrib><description>The introduction of type b Haemophilus influenzae conjugate vaccines into routine vaccination schedules has significantly reduced the burden of this disease; however, widespread use in developing countries is constrained by vaccine costs, and there is a need for a simple and high-yielding manufacturing process. The vaccine is composed of purified capsular polysaccharide conjugated to an immunogenic carrier protein. To improve the yield and rate of the reductive amination conjugation reaction used to make this vaccine, some of the carboxyl groups of the carrier protein, tetanus toxoid, were modified to hydrazides, which are more reactive than the ε -amine of lysine. Other reaction parameters, including the ratio of the reactants, the size of the polysaccharide, the temperature and the salt concentration, were also investigated. Experimental design was used to minimize the number of experiments required to optimize all these parameters to obtain conjugate in high yield with target characteristics. It was found that increasing the reactant ratio and decreasing the size of the polysaccharide increased the polysaccharide:protein mass ratio in the product. Temperature and salt concentration did not improve this ratio. These results are consistent with a diffusion controlled rate limiting step in the conjugation reaction. Excessive modification of tetanus toxoid with hydrazide was correlated with reduced yield and lower free polysaccharide. This was attributed to a greater tendency for precipitation, possibly due to changes in the isoelectric point. Experimental design and multiple regression helped identify key parameters to control and thereby optimize this conjugation reaction.</description><identifier>ISSN: 0282-0080</identifier><identifier>EISSN: 1573-4986</identifier><identifier>DOI: 10.1007/s10719-011-9344-3</identifier><identifier>PMID: 21850577</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Algorithms ; Amines - chemistry ; Amines - immunology ; Bacterial Capsules - immunology ; Biochemistry ; Biomedical and Life Sciences ; Capsular polysaccharides ; Design optimization ; Developing Countries ; Diffusion ; Drug therapy ; glycoconjugates ; Haemophilus Infections - immunology ; Haemophilus Infections - prevention &amp; control ; Haemophilus influenzae ; Haemophilus influenzae type b - immunology ; Haemophilus influenzae type b - pathogenicity ; Haemophilus Vaccines - chemical synthesis ; Haemophilus Vaccines - immunology ; Humans ; Hydrazines - chemistry ; Hydrazines - immunology ; Immunoconjugates - chemistry ; Immunogenicity ; Influenza ; Isoelectric points ; Life Sciences ; Lysine ; Lysine - chemistry ; Lysine - immunology ; Pathology ; Polysaccharides - chemistry ; Polysaccharides - immunology ; Polysaccharides, Bacterial - chemistry ; Polysaccharides, Bacterial - immunology ; Precipitation ; Research Design ; Salts ; Temperature effects ; Tetanus ; Tetanus Toxoid - chemistry ; Tetanus Toxoid - immunology ; Vaccination ; Vaccines ; Vaccines, Conjugate - chemistry ; Vaccines, Conjugate - immunology</subject><ispartof>Glycoconjugate journal, 2011-10, Vol.28 (7), p.463-472</ispartof><rights>Springer Science+Business Media, LLC 2011</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-e9a439006f95f216d64d14cc7528e203e1d88b02e8ed2ae2d9eb51ce93c3d5903</citedby><cites>FETCH-LOGICAL-c402t-e9a439006f95f216d64d14cc7528e203e1d88b02e8ed2ae2d9eb51ce93c3d5903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10719-011-9344-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10719-011-9344-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,782,786,27931,27932,41495,42564,51326</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21850577$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Laferriere, Craig</creatorcontrib><creatorcontrib>Ravenscroft, Neil</creatorcontrib><creatorcontrib>Wilson, Seanette</creatorcontrib><creatorcontrib>Combrink, Jill</creatorcontrib><creatorcontrib>Gordon, Lizelle</creatorcontrib><creatorcontrib>Petre, Jean</creatorcontrib><title>Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid</title><title>Glycoconjugate journal</title><addtitle>Glycoconj J</addtitle><addtitle>Glycoconj J</addtitle><description>The introduction of type b Haemophilus influenzae conjugate vaccines into routine vaccination schedules has significantly reduced the burden of this disease; however, widespread use in developing countries is constrained by vaccine costs, and there is a need for a simple and high-yielding manufacturing process. The vaccine is composed of purified capsular polysaccharide conjugated to an immunogenic carrier protein. To improve the yield and rate of the reductive amination conjugation reaction used to make this vaccine, some of the carboxyl groups of the carrier protein, tetanus toxoid, were modified to hydrazides, which are more reactive than the ε -amine of lysine. Other reaction parameters, including the ratio of the reactants, the size of the polysaccharide, the temperature and the salt concentration, were also investigated. Experimental design was used to minimize the number of experiments required to optimize all these parameters to obtain conjugate in high yield with target characteristics. It was found that increasing the reactant ratio and decreasing the size of the polysaccharide increased the polysaccharide:protein mass ratio in the product. Temperature and salt concentration did not improve this ratio. These results are consistent with a diffusion controlled rate limiting step in the conjugation reaction. Excessive modification of tetanus toxoid with hydrazide was correlated with reduced yield and lower free polysaccharide. This was attributed to a greater tendency for precipitation, possibly due to changes in the isoelectric point. Experimental design and multiple regression helped identify key parameters to control and thereby optimize this conjugation reaction.</description><subject>Algorithms</subject><subject>Amines - chemistry</subject><subject>Amines - immunology</subject><subject>Bacterial Capsules - immunology</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Capsular polysaccharides</subject><subject>Design optimization</subject><subject>Developing Countries</subject><subject>Diffusion</subject><subject>Drug therapy</subject><subject>glycoconjugates</subject><subject>Haemophilus Infections - immunology</subject><subject>Haemophilus Infections - prevention &amp; control</subject><subject>Haemophilus influenzae</subject><subject>Haemophilus influenzae type b - immunology</subject><subject>Haemophilus influenzae type b - pathogenicity</subject><subject>Haemophilus Vaccines - chemical synthesis</subject><subject>Haemophilus Vaccines - immunology</subject><subject>Humans</subject><subject>Hydrazines - chemistry</subject><subject>Hydrazines - immunology</subject><subject>Immunoconjugates - chemistry</subject><subject>Immunogenicity</subject><subject>Influenza</subject><subject>Isoelectric points</subject><subject>Life Sciences</subject><subject>Lysine</subject><subject>Lysine - chemistry</subject><subject>Lysine - immunology</subject><subject>Pathology</subject><subject>Polysaccharides - chemistry</subject><subject>Polysaccharides - immunology</subject><subject>Polysaccharides, Bacterial - chemistry</subject><subject>Polysaccharides, Bacterial - immunology</subject><subject>Precipitation</subject><subject>Research Design</subject><subject>Salts</subject><subject>Temperature effects</subject><subject>Tetanus</subject><subject>Tetanus Toxoid - chemistry</subject><subject>Tetanus Toxoid - immunology</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Vaccines, Conjugate - chemistry</subject><subject>Vaccines, Conjugate - immunology</subject><issn>0282-0080</issn><issn>1573-4986</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kT1vFDEQhi0EIkfCD6BBFg2VYez9sksUJQQpUpqktnz27J1Pu_ay9obcdfxzfLoAEhKVi3ned6x5CHnH4RMH6D4nDh1XDDhnqqprVr0gK950FauVbF-SFQgpGICEM_ImpR2UTC3ka3ImuGyg6boV-Xn1NOHsRwzZDNRh8ptAc6Rxyn70B6Qm0BuDY5y2flgS9aEfFgwHgzTvJ6RramPYLRuTkT4aa31AOhqH9IfPW7rdu9kcvEPmypJHk0ujoxmzCaUrx6fo3QV51Zsh4dvn95w8XF_dX96w27uv3y6_3DJbg8gMlakrBdD2qukFb11bO15b2zVCooAKuZNyDQIlOmFQOIXrhltUla1co6A6Jx9PvdMcvy-Ysh59sjgMJmBcklbllh2Xsinkh3_IXVzmUD6npap5qzo4QvwE2TmmNGOvp3JGM-81B320o092dLGjj3Z0VTLvn4uX9YjuT-K3jgKIE5DKKGxw_rv5_62_AJFEnMQ</recordid><startdate>20111001</startdate><enddate>20111001</enddate><creator>Laferriere, Craig</creator><creator>Ravenscroft, Neil</creator><creator>Wilson, Seanette</creator><creator>Combrink, Jill</creator><creator>Gordon, Lizelle</creator><creator>Petre, Jean</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7QL</scope><scope>7U9</scope><scope>C1K</scope></search><sort><creationdate>20111001</creationdate><title>Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid</title><author>Laferriere, Craig ; Ravenscroft, Neil ; Wilson, Seanette ; Combrink, Jill ; Gordon, Lizelle ; Petre, Jean</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c402t-e9a439006f95f216d64d14cc7528e203e1d88b02e8ed2ae2d9eb51ce93c3d5903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Algorithms</topic><topic>Amines - chemistry</topic><topic>Amines - immunology</topic><topic>Bacterial Capsules - immunology</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Capsular polysaccharides</topic><topic>Design optimization</topic><topic>Developing Countries</topic><topic>Diffusion</topic><topic>Drug therapy</topic><topic>glycoconjugates</topic><topic>Haemophilus Infections - immunology</topic><topic>Haemophilus Infections - prevention &amp; control</topic><topic>Haemophilus influenzae</topic><topic>Haemophilus influenzae type b - immunology</topic><topic>Haemophilus influenzae type b - pathogenicity</topic><topic>Haemophilus Vaccines - chemical synthesis</topic><topic>Haemophilus Vaccines - immunology</topic><topic>Humans</topic><topic>Hydrazines - chemistry</topic><topic>Hydrazines - immunology</topic><topic>Immunoconjugates - chemistry</topic><topic>Immunogenicity</topic><topic>Influenza</topic><topic>Isoelectric points</topic><topic>Life Sciences</topic><topic>Lysine</topic><topic>Lysine - chemistry</topic><topic>Lysine - immunology</topic><topic>Pathology</topic><topic>Polysaccharides - chemistry</topic><topic>Polysaccharides - immunology</topic><topic>Polysaccharides, Bacterial - chemistry</topic><topic>Polysaccharides, Bacterial - immunology</topic><topic>Precipitation</topic><topic>Research Design</topic><topic>Salts</topic><topic>Temperature effects</topic><topic>Tetanus</topic><topic>Tetanus Toxoid - chemistry</topic><topic>Tetanus Toxoid - immunology</topic><topic>Vaccination</topic><topic>Vaccines</topic><topic>Vaccines, Conjugate - chemistry</topic><topic>Vaccines, Conjugate - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Laferriere, Craig</creatorcontrib><creatorcontrib>Ravenscroft, Neil</creatorcontrib><creatorcontrib>Wilson, Seanette</creatorcontrib><creatorcontrib>Combrink, Jill</creatorcontrib><creatorcontrib>Gordon, Lizelle</creatorcontrib><creatorcontrib>Petre, Jean</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>Proquest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Glycoconjugate journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Laferriere, Craig</au><au>Ravenscroft, Neil</au><au>Wilson, Seanette</au><au>Combrink, Jill</au><au>Gordon, Lizelle</au><au>Petre, Jean</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid</atitle><jtitle>Glycoconjugate journal</jtitle><stitle>Glycoconj J</stitle><addtitle>Glycoconj J</addtitle><date>2011-10-01</date><risdate>2011</risdate><volume>28</volume><issue>7</issue><spage>463</spage><epage>472</epage><pages>463-472</pages><issn>0282-0080</issn><eissn>1573-4986</eissn><abstract>The introduction of type b Haemophilus influenzae conjugate vaccines into routine vaccination schedules has significantly reduced the burden of this disease; however, widespread use in developing countries is constrained by vaccine costs, and there is a need for a simple and high-yielding manufacturing process. The vaccine is composed of purified capsular polysaccharide conjugated to an immunogenic carrier protein. To improve the yield and rate of the reductive amination conjugation reaction used to make this vaccine, some of the carboxyl groups of the carrier protein, tetanus toxoid, were modified to hydrazides, which are more reactive than the ε -amine of lysine. Other reaction parameters, including the ratio of the reactants, the size of the polysaccharide, the temperature and the salt concentration, were also investigated. Experimental design was used to minimize the number of experiments required to optimize all these parameters to obtain conjugate in high yield with target characteristics. It was found that increasing the reactant ratio and decreasing the size of the polysaccharide increased the polysaccharide:protein mass ratio in the product. Temperature and salt concentration did not improve this ratio. These results are consistent with a diffusion controlled rate limiting step in the conjugation reaction. Excessive modification of tetanus toxoid with hydrazide was correlated with reduced yield and lower free polysaccharide. This was attributed to a greater tendency for precipitation, possibly due to changes in the isoelectric point. Experimental design and multiple regression helped identify key parameters to control and thereby optimize this conjugation reaction.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>21850577</pmid><doi>10.1007/s10719-011-9344-3</doi><tpages>10</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0282-0080
ispartof Glycoconjugate journal, 2011-10, Vol.28 (7), p.463-472
issn 0282-0080
1573-4986
language eng
recordid cdi_proquest_miscellaneous_907171885
source MEDLINE; SpringerNature Journals
subjects Algorithms
Amines - chemistry
Amines - immunology
Bacterial Capsules - immunology
Biochemistry
Biomedical and Life Sciences
Capsular polysaccharides
Design optimization
Developing Countries
Diffusion
Drug therapy
glycoconjugates
Haemophilus Infections - immunology
Haemophilus Infections - prevention & control
Haemophilus influenzae
Haemophilus influenzae type b - immunology
Haemophilus influenzae type b - pathogenicity
Haemophilus Vaccines - chemical synthesis
Haemophilus Vaccines - immunology
Humans
Hydrazines - chemistry
Hydrazines - immunology
Immunoconjugates - chemistry
Immunogenicity
Influenza
Isoelectric points
Life Sciences
Lysine
Lysine - chemistry
Lysine - immunology
Pathology
Polysaccharides - chemistry
Polysaccharides - immunology
Polysaccharides, Bacterial - chemistry
Polysaccharides, Bacterial - immunology
Precipitation
Research Design
Salts
Temperature effects
Tetanus
Tetanus Toxoid - chemistry
Tetanus Toxoid - immunology
Vaccination
Vaccines
Vaccines, Conjugate - chemistry
Vaccines, Conjugate - immunology
title Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-05T09%3A03%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Experimental%20design%20to%20optimize%20an%20Haemophilus%20influenzae%20type%20b%20conjugate%20vaccine%20made%20with%20hydrazide-derivatized%20tetanus%20toxoid&rft.jtitle=Glycoconjugate%20journal&rft.au=Laferriere,%20Craig&rft.date=2011-10-01&rft.volume=28&rft.issue=7&rft.spage=463&rft.epage=472&rft.pages=463-472&rft.issn=0282-0080&rft.eissn=1573-4986&rft_id=info:doi/10.1007/s10719-011-9344-3&rft_dat=%3Cproquest_cross%3E2469097911%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=894169705&rft_id=info:pmid/21850577&rfr_iscdi=true